AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice

Am J Physiol Lung Cell Mol Physiol. 2018 Sep 1;315(3):L382-L386. doi: 10.1152/ajplung.00185.2018. Epub 2018 May 10.

Abstract

We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPCs). To investigate whether a limited availability of HPCs may contribute to CS-induced lung injury, we used a Food and Drug Administration-approved antagonist of the interactions of stromal cell-derived factor 1 (SDF-1) with its chemokine receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 wk. AMD3100 treatment did not affect either lung SDF-1 levels, which were reduced by CS, or lung inflammatory cell counts. However, AMD3100 markedly improved CS-induced bone marrow HPC suppression and significantly ameliorated emphysema-like end points, such as alveolar airspace size, lung volumes, and lung static compliance. These results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema.

Keywords: COPD; bone marrow; emphysema; lung treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Chemokine CXCL12 / antagonists & inhibitors
  • Chemokine CXCL12 / metabolism
  • Cyclams
  • Female
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Heterocyclic Compounds / pharmacology*
  • Lung Injury* / etiology
  • Lung Injury* / metabolism
  • Lung Injury* / pathology
  • Lung Injury* / prevention & control
  • Mice
  • Pulmonary Alveoli / metabolism*
  • Pulmonary Alveoli / pathology
  • Pulmonary Emphysema* / etiology
  • Pulmonary Emphysema* / metabolism
  • Pulmonary Emphysema* / pathology
  • Pulmonary Emphysema* / prevention & control
  • Receptors, CXCR4 / metabolism
  • Smoking* / adverse effects
  • Smoking* / metabolism
  • Smoking* / pathology

Substances

  • Benzylamines
  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Cyclams
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • plerixafor